St. John's Wort for Major Depressive Disorder: A Systematic Review

RAND researchers conducted a systematic review that synthesized evidence from randomized controlled trials of St. John's wort (SJW)-used adjunctively or as monotherapy-to provide estimates of its efficacy and safety in treating adults with major depressive disorder. Outcomes of interest included changes in depressive symptomatology, quality of life, and adverse effects. Efficacy meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. In total, 35 studies met inclusion criteria. There is moderate evidence, due to unexplained heterogeneity between studies, that depression improvement based on the number of treatment responders and depression scale scores favors SJW over placebo, and results are comparable to antidepressants. The existing evidence is based on studies testing SJW as monotherapy; there is a lack of evidence for SJW given as adjunct therapy to standard antidepressant therapy. We found no systematic difference between SJW extracts, but head-to-head trials are missing; LI 160 (0.3% hypericin, 1-4% hyperforin) was the extract with the greatest number of studies. Only two trials assessed quality of life. SJW adverse events reported in included trials were comparable to placebo, and were fewer compared with antidepressant medication; however, adverse event assessments were limited, and thus we have limited confidence in this conclusion.